Immunomodulatory Effect of Pentoxifylline in Suppressing Experimental Autoimmune Myocarditis

Although a recent clinical study reported the beneficial effects of pentoxifylline (PTX), a phosphodiesterase inhibitor, on both symptoms and cardiac function in dilated cardiomyopathy (DCM), the precise mechanism of the drug has not been delineated. This study examined the efficacy of PTX in the tr...

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Bibliographic Details
Published in:Circulation Journal 2002, Vol.66(5), pp.499-504
Main Authors: Takehana, Hitoshi, Inomata, Takayuki, Niwano, Hiroe, Nishii, Mototsugu, Matsuda, Chieko, Kohno, Ken, Machida, Yoji, Izumi, Tohru
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - therapeutic use
Animals
Autoimmune disease
Autoimmune Diseases - drug therapy
Autoimmune Diseases - immunology
Autoimmune Diseases - metabolism
Autoimmune Diseases - pathology
Biological and medical sciences
Cell Division - drug effects
Cytokines
Cytokines - biosynthesis
Dilated cardiomyopathy
Female
Immunomodulators
In Vitro Techniques
Medical sciences
Myocarditis
Myocarditis - drug therapy
Myocarditis - immunology
Myocarditis - metabolism
Myocarditis - pathology
Myocardium - metabolism
Pentoxifylline
Pentoxifylline - therapeutic use
Pharmacology. Drug treatments
Rats
Rats, Inbred Lew
Severity of Illness Index
T-Lymphocytes - immunology
T-Lymphocytes - pathology
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Summary:Although a recent clinical study reported the beneficial effects of pentoxifylline (PTX), a phosphodiesterase inhibitor, on both symptoms and cardiac function in dilated cardiomyopathy (DCM), the precise mechanism of the drug has not been delineated. This study examined the efficacy of PTX in the treatment of experimental autoimmune myocarditis (EAM), as a model of the autoimmune mechanism involved in DCM. Oral PTX, or saline as control, was administered to Lewis rats at 150 mg/kg body weight per day bid daily from 5 days before immunization with cardiac myosin until death on Day 21. Histological examination of the hearts showed PTX significantly reduced the severity of EAM. mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and IL-10 was significantly reduced in peripheral blood mononuclear cells, but expression of IL-4 and IL-6 was upregulated in heart tissue. PTX in vitro could suppress T cell proliferation and inhibit TNF-α and interferon-γ production. In conclusion, the immunomodulatory effects of PTX had a significant therapeutic result in EAM. This is the first report to describe such an effect of PTX in a specific animal model for DCM. (Circ J 2002; 66: 499 - 504)
ISSN:1346-9843
1347-4820
DOI:10.1253/circj.66.499